26 research outputs found

    Adaptive evolution and inherent tolerance to extreme thermal environments

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    <p>Abstract</p> <p>Background</p> <p>When introduced to novel environments, the ability for a species to survive and rapidly proliferate corresponds with its adaptive potential. Of the many factors that can yield an environment inhospitable to foreign species, phenotypic response to variation in the thermal climate has been observed within a wide variety of species. Experimental evolution studies using bacteriophage model systems have been able to elucidate mutations, which may correspond with the ability of phage to survive modest increases/decreases in the temperature of their environment.</p> <p>Results</p> <p>Phage ΦX174 was subjected to both elevated (50°C) and extreme (70°C+) temperatures for anywhere from a few hours to days. While no decline in the phage's fitness was detected when it was exposed to 50°C for a few hours, more extreme temperatures significantly impaired the phage; isolates that survived these heat treatments included the acquisition of several mutations within structural genes. As was expected, long-term treatment of elevated and extreme temperatures, ranging from 50-75°C, reduced the survival rate even more. Isolates which survived the initial treatment at 70°C for 24 or 48 hours exhibited a significantly greater tolerance to subsequent heat treatments.</p> <p>Conclusions</p> <p>Using the model organism ΦX174, we have been able to study adaptive evolution on the molecular level under extreme thermal changes in the environment, which to-date had yet to be thoroughly examined. Under both acute and extended thermal selection, we were able to observe mutations that occurred in response to excessive external pressures independent of concurrently evolving hosts. Even though its host cannot tolerate extreme temperatures such as the ones tested here, this study confirms that ΦX174 is capable of survival.</p

    The Evolution of Molecular Compatibility between Bacteriophage ΦX174 and its Host

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    Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture. Engineered to include codons with a lesser usage and/or tRNA abundance within the host, three different attenuated strains of the bacterial virus ФX174 were created and propagated via serial transfers. Molecular sequence data indicate that biosynthetic compatibility was recovered rapidly. Extensive computational simulations were performed to assess the role of mutational biases as well as selection for translational efficiency in the engineered phage. Using bacteriophage as a model system, we can begin to unravel the evolutionary processes shaping codon compatibility between viruses and their host

    Evolution of the Sequence Composition of Flaviviruses

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    The adaption of pathogens to their host(s) is a major factor in the emergence of infectious disease and the persistent survival of many of the infectious diseases within the population. Since many of the smaller viral pathogens are entirely dependent upon host machinery, it has been postulated that they are under selection for a composition similar to that of their host. Analyses of sequence composition have been conducted for numerous small viral species including the Flavivirus genus. Examination of the species within this particular genus that infect vertebrate hosts revealed that sequence composition proclivities do not correspond with vector transmission as the evolutionary history of this species suggests. Recent sequencing efforts have generated complete genomes for many viral species including members of the Flavivirus genus. A thorough comparison of the sequence composition was conducted for all of the available Flaviviruses for which the complete genome is publicly available. This effort expands the work of previous studies to include new vector-borne species as well as members of the insect-specific group which previously have not been explored. Metrics, including mono-, di-, and trinucleotide abundances as well as NC values and codon usage preferences, were explored both for the entire polyprotein sequence as well as for each individual coding region. Preferences for compositions correspond to host-range rather than evolutionary history; species which infect vertebrate hosts exhibited particular preferences similar to each other as well as in correspondence with their host’s preferences. Flaviviruses which do not infect vertebrate hosts, however, did not show these proclivities, with the exception of the Kamiti River virus suggesting its recent (either past or present) infectivity of an unknown vertebrate host

    Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome

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    Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/human​n. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies.National Institutes of Health (U.S.) (U54HG004968

    A framework for human microbiome research

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    A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

    Structure, function and diversity of the healthy human microbiome

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    Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University
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